纹状体 D2 受体的过度表达会降低动机,从而减少食物预期活动。

Overexpression of striatal D2 receptors reduces motivation thereby decreasing food anticipatory activity.

机构信息

Department of Psychology, Barnard College, New York City, New York.

Department of Psychiatry, Columbia University, New York City, New York.

出版信息

Eur J Neurosci. 2020 Jan;51(1):71-81. doi: 10.1111/ejn.14219. Epub 2018 Nov 26.

Abstract

Dopamine has been implicated in circadian timing underlying the food entrainable oscillator (FEO) circuitry and overexpression of the dopamine D2 receptor (D2R) in the striatum has been reported to reduce motivation to obtain food rewards in operant tasks. In the present study, we explored both of these mechanisms by examining food anticipatory activity (FAA) in dopamine D2 receptor-overexpressing (D2R-OE) mice under various durations of food availability. First, we noted that at baseline, there were no differences between D2R-OE mice and their littermates in activity level, food intake, and body weight or in circadian activity. Under conditions of very restricted food availability (4 or 6 hr), both genotypes displayed FAA. In contrast, under 8-hr food availability, control mice showed FAA, but D2R-OE mice did not. Normalization of D2R by administration of doxycycline, a tetracycline analogue, rescued FAA under 8-hr restricted food. We next tested for circadian regulation of FAA. When given ad libitum access to food, neither D2R-OE nor controls were active during the daytime. However, after an interval of food restriction, all mice showed elevated locomotor activity at the time of previous food availability in the day, indicating circadian timing of anticipatory activity. In summary, motivation is reduced in D2R-OE mice but circadian timing behavior is not affected. We conclude that an increase in striatal D2R reduces FAA by modulating motivation and not by acting on a clock mechanism.

摘要

多巴胺与食物可诱导振荡器(FEO)电路的昼夜节律计时有关,纹状体中多巴胺 D2 受体(D2R)的过表达已被报道会降低操作任务中获得食物奖励的动机。在本研究中,我们通过检查多巴胺 D2 受体过表达(D2R-OE)小鼠在不同食物供应时间下的食物预期活动(FAA),探讨了这两种机制。首先,我们注意到在基线时,D2R-OE 小鼠与其同窝仔鼠在活动水平、食物摄入、体重或昼夜节律活动方面没有差异。在食物供应非常有限的情况下(4 或 6 小时),两种基因型都显示出 FAA。相比之下,在 8 小时的食物供应下,对照小鼠表现出 FAA,但 D2R-OE 小鼠没有。用强力霉素(一种四环素类似物)对 D2R 进行归一化,可在 8 小时的限时进食条件下挽救 FAA。接下来,我们测试了 FAA 的昼夜节律调节。当给予自由摄取食物时,D2R-OE 和对照小鼠在白天都不活跃。然而,在一段时间的食物限制后,所有小鼠在白天之前的食物供应时间都表现出更高的运动活性,表明预期活动具有昼夜节律计时。总之,D2R-OE 小鼠的动机降低,但昼夜节律计时行为不受影响。我们得出的结论是,纹状体中 D2R 的增加通过调节动机而不是通过作用于时钟机制来减少 FAA。

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